hemolytic anemia final presentation.pptx

approach to hemolytic anemia

1. APPROACH TO A CASE OF HEMOLYTIC ANEMIA

2. HISTORY: Age of the patient Gender of patient Address Common presenting features: Easy fatigability on exertion Breathlessness Paleness Bleeding from injured sites, spontaneous bleeding Other features: Abdominal pain, pain in the limbs, headache Convulsion, hemiplegia Fever Haematuria, dark-coloured urine, yellow-coloured urine Yellowish pigmentation of the eyes and body Precipitating factors: Certain food products- Fava beans Drug exposure: Beta lactamase inhibitors, ceftriaxone, IVIG, methlydopa, NSAIDs, Dapsone, nitrofurantoin, ibuprofen, interferon, mefloquine, metronidazole Past history: Previous blood transfusion History of neonatal jaundice, phototherapy Family history: Blood disorders in family in siblings Sibling death, abortions, stillbirths History of cholelithiasis, jaundice, splenectomy Consanguinity Travel history: Endemic areas with malaria

3. On Examination: General condition Pallor, icterus, cyanosis , ly mphadenopathy , e dema Mongoloid facies, short stature Skull bossing (prominent forehead), maxilla, flat nasal bridge, separated teeth Leukonychia, koilonychia Ankle ulcers Petechial rashes

4. Anthropometry Vitals: Heart rate, respiratory rate, temperature, b lood p ressure Systemic findings: Cardiovascular system: heart sounds, murmur, bruit, pericardial rub Respiratory system: air entry, added sounds Per abdomen: tenderness, distension, ascites, bowel sounds CNS: Delerium , Tone, Power, Reflex INVESTIGATIONS: Complete blood count Peripheral blood study-type of anaemia , presence of abnormal cells; sickle cells in sickle-cell anaemia , spherocytes in spherocytosis, basophilic stippling in thalassemia and lead poisoning, fragmented red blood cells in haemolytic uremic syndrome, Heinz bodies and Howell-Jolly bodies Evidence of haemolysi s --r e ticulocytosis . Polychromasia and basophil stippling are indirect evidence of reticulocytosis . LDH

5. Type of cell Disease Sickle cells Sickle cell disease Target cells Hemoglobinopathies (HbC, HbS, thalassemia), liver disease Schistocytes/burr cells/helmet cells/RBC fragments Microangiopathic hemolytic anemia (DIC, HUS, TTP), Venoms Spherocytes Hereditary spherocytosis, autoimmune hemolytic anemia Cigar-shaped cells Hereditary elliptocytosis “Bite” cells G6PD deficiency Poikilocytosis, microcytosis, fragmented erythrocytes, elliptocytes Hereditary pyropoikilocytosis Basophillic stippling Thalessemia, Lead

6. MCV, MCH, Reticulocyte count Na, K, Ur, Cr, Rbs Urine analysis (routine and urobilinogen level) Stool culture LFT (Tb, DB, ALP) Haptoglobin, LDH Osmotic fragility test Hb electrophoresis Direct antiglobulin test Iron profile( ferritin, transferrin level, TIBC) Bone marrow X-ray skull, X-ray hand, X-ray chest USG Cranium, MRI

7. INTRODUCTION Hemolysis is defined as the premature destruction of red blood cells .

8. Intrinsic Hemolysis Hemoglobinopathies • α-Thalassemias, β-Thalassemias • Sickle cell disease • Unstable hemoglobins RBC Membrane Defects • Hereditary spherocytosis • Hereditary elliptocytosis, pyropoikilocytosis Hereditary stomatocytosis syndromes Enzymopathies HMP shunt abnormality Glucose-6-phosphate dehydrogenase Pyruvate kinase Hexokinase Phosphofructokinase Extrinsic Hemolysis Immune Mediated Primary • Warm-reactive autoimmune hemolytic anemia • Alloimmune hemolytic anemia • Acute and Delayed Hemolytic transfusion reaction • Drug-induced hemolytic anemias Secondary • Evans syndrome • Primary or Acquired immunodeficiency • Malignancy (lymphoproliferative disorders: lymphomas) • Infection or Post-transplant Cold Agglutinins • Primary • Secondary: Infection (e.g., Mycoplasma , EBV syphilis), Malignancy,Mixed :SLE and other rheumatology disorders • Paroxysmal cold hemoglobinuria (Immune or Post-infectious) Other • Spider venom,Toxins: arsenic, lead, copper CLASSIFICATION

9. THALASSEMIA Beta Thalassemia: Beta thalassemia usually caused by genes mutation on chromosome 11 Thalassemia major ( Cooley’s Anemia): e.g. severe B+/B+ mutations, B+/B0, B0/B0 Thalassemia Intermedia: e.g. B+/B0, B+/B+) Some rare cases also exist in which both beta and alpha mutations coexist. Thalassemia minor (Beta Thalassemia carrier/trait): e.g. B+/B, B0/B Alpha Thalassemia: • α thalassemia usually caused by gene mutation on C hromosome 16 .

10. HbE is an abnormal hemoglobin resulting from a qualitative mutation in the β- globin gene and is the 2nd most common globin mutation worldwide. It can be associated with beta thalassemia Investigation Hemoglobin, Red cell count, reticulocyte count RBC indices – MCV & MCH,MCH, RDW Peripheral blood smear Haptoglobulin and hemopexin B.M. study: hyperplastic erythropoiesis Treatment: Transfusions should generally be given at intervals of 3-4 wk Chelation Therapy: Deferoxamine,Deferasirox BM transplantation, gene therapy

11. SICKLE CELL ANEMIA Point mutation in β-globin gene , single amino acid substitution (glutamic acid to valine). Mutant HbA is termed HbS . Newborns are initially asymptomatic because of high HbF Heterozygotes (sickle cell trait) have resistance to malaria. Most common autosomal recessive disease in Black population. Hb electrophoresis Treatment: hydroxyurea , hydration.

12. HEREDITARY SPHEROCYTOSIS Primarily autosomal dominant. Due to defect in proteins interacting with RBC membrane skeleton and plasma membrane (eg, ankyrin, band 3, protein 4.2, spectrin) Splenomegaly, pigmented gallstones, aplastic crisis (parvovirus B19 infection). Labs: Decreased mean fluorescence of RBCs in eosin 5-maleimide (EMA) binding test, increased fragility in osmotic fragility test. Treatment: splenectomy

13. GLUCOSE 6 PHOSPHATE DEHYDROGENASE DEFICIENCY X-linked Recessive WHO classification: Class I variants: lowest enzyme activity and cause the most severe disease, Class II variants: severe deficiency and intermittent hemolysis (Mediterranean) Class III variants: demonstrate moderate enzyme deficiency and intermittent hemolysis. Clinical Features: Infancy: Jaundice usually develops in the first postnatal days Beyond infancy: fatigue, back pain, dark urine, and jaundice Investigation: HB-anemia, reticulocytosis , high unconjugated bilirubin and lactate dehydrogenase, and decreased haptoglobin . Treatment: Hemolytic episodes are self-limited, but sometimes require transfusion for severe anemia. G6PDdeficient patients benefit from counseling regarding avoidance of oxidative triggers

14. PYRUVATE KINASE DEFICIENCY

15. PAROXYSMAL NOCTURNAL HEMATURIA Triad: Coombs ⊝ hemolytic anemia, pancytopenia, venous thrombosis (eg, Budd_x0002_Chiari syndrome). Labs: CD55/59 ⊝ RBCs on flow cytometry. Treatment: eculizumab (targets terminal complement protein C5).

16. REFERENCES Nelson’s Textbook of Pediatrics, 21 st edition National Guidelines for Thalassemia and Sickle Cell Anemia 2074 USMLE First Aid 2020 Uptodate 2023

17. THANK YOU